Valerian root • Primrose flower & leaf • California Poppy flower & leaf • Hops strobile • Wild Lettuce • Passion Flower • Scullcap • Grain alcohol & Distilled Water.
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Below is general information about the effectiveness of the known ingredients contained in the product Valerian-Primrose Virtue. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of wild lettuce.
Below is general information about the safety of the known ingredients contained in the product Valerian-Primrose Virtue. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Oral Baikal skullcap 0.5-3.52 grams daily has been used with apparent safety for up to 8 weeks (92776,101738,101739,110023). However, a high quality assessment of safety has not been conducted. A specific product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been associated with an increased risk for liver and lung injury. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination. There is insufficient reliable information available about the safety of Baikal skullcap when used intravenously or topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
There is insufficient reliable information available about the safety of California poppy.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally. Cowslip has been used with apparent safety in combination with other herbs (SinuComp, Sinupret, Sinupret +, Bronchipret) (374,379,13557).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Evening primrose oil has been used safely in doses up to 6 grams daily for up to 1 year (7566,7567,8926,12036,20512,49286,49360,109426). There is insufficient reliable information available about the safety of evening primrose oil when used topically. There is also insufficient reliable information available about the safety of evening primrose seed, flower, or leaf when used orally or topically.
CHILDREN: POSSIBLY SAFE
when evening primrose oil is used orally and appropriately, short-term.
In children up to 5 years of age, doses of evening primrose oil up to 3 grams daily have been used safely for 5 months (20512,49273), and 0.5 grams/kg daily has been used safely for 8 weeks (7570). In children up to 12 years of age, doses of 4-6 grams daily have been used safely for 3-5 months (7565,7566,20512,49286). ...when used topically and appropriately, short-term. In children 2-10 years of age, evening primrose oil has been applied to affected areas of the skin twice daily for up to 3 months (96718). There is insufficient reliable information available about the safety of evening primrose seed, flower, or leaf when used orally or topically.
PREGNANCY: POSSIBLY SAFE
when evening primrose oil is used orally and appropriately.
In small studies of evening primrose oil for pre-eclampsia, 4 grams has been used orally daily for up to 10 weeks during pregnancy with apparent safety (1409,20525). ...when evening primrose oil is used orally or intravaginally to improve cervical ripening. Evening primrose oil has been used safely during the last 1-3 weeks of pregnancy to improve cervical ripening (20524,96717,112130,112131). Intravaginally, evening primrose oil 500-1000 mg as either a single dose or administered daily starting at week 38 until pregnancy has been used with apparent safety for this purpose (112130,112131). Orally, evening primrose oil 1500-4500 mg in divided doses daily for 1-3 weeks has been used with apparent safety for this purpose, although one study found 5 cases of meconium-stained amniotic fluid (112131). Some studies report that improvement was lacking and there was a trend toward prolonged labor, prolonged rupture of membranes, increased rates of arrest of descent, and increased oxytocin requirements (1411,112131). Evening primrose oil has also been linked to a case report of petechiae and ecchymoses in a newborn infant whose mother took a total of 6.5 grams during the week before giving birth (16303); use with caution, especially in high doses.
LACTATION: POSSIBLY SAFE
when evening primrose oil is used orally.
Supplementation with evening primrose oil during lactation results in the secretion of high levels of the constituent gamma linolenic acid into breast milk (1982); however, this fatty acid is normally present in significant amounts in breast milk (11884).
LIKELY SAFE ...when consumed in amounts commonly found in foods. Hops extract and hops oil have Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when hops extract and hops-derived bitter acids are used orally and appropriately for medicinal purposes, short-term. Hops extract has been used with apparent safety in doses of up to 300 mg daily for 2-3 months. Hops-derived bitter acids have been used with apparent safety at a dose of 35 mg daily for 3 months (12,55338,55370,102899,105953,107813).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally as a flavoring in foods. The US Food and Drug Administration (FDA) lists passion flower as a permitted food flavoring additive, to be used in the minimum quantity necessary (91203).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Passion flower extract has been used with apparent safety at doses up to 800 mg daily for up to 8 weeks (88198,102866). A specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) has been safely used at a dose of 45 drops daily for up to one month (8007,95036). Also, a tea prepared by steeping 2 grams of the dried aerial parts of passion flower in 250 mL of boiling water for 10 minutes has been used nightly for 7 nights (17374). There is insufficient reliable information available about the safety of passion flower when used topically.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
A specific passion flower product (Pasipay, Iran Darouk Pharmaceutical Company) has been used safely in children aged 6-13 years at a dose of 0.04 mg/ kg daily for 8 weeks (88197).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Some case reports suggest that passion flower use during the first and second trimesters of pregnancy may be associated with an increased risk for premature rupture of membranes and meconium aspiration syndrome; however, causality has not been confirmed (97279). The alkaloids harman and harmaline, which are sometimes found in passion flower, have been reported to have uterine stimulant activity (4,11020,95037). It is not known whether these constituents are present in sufficient quantities to have an effect.
LACTATION:
Insufficient reliable information available; avoid using.
There is insufficient reliable information available about the safety of skullcap.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately, short-term. Valerian 300-600 mg daily has been safely used in clinical studies in over 12,000 patients for up to 6 weeks (2074,3484,3485,4032,15018,17577,17578,19409,96242,103221)(104010,105718). There is insufficient reliable information available about the safety of valerian when used orally for longer than 6 weeks.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Valerian 160-320 mg has been used with apparent safety in children under 12 years of age for 4-8 weeks (14416).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when mature, properly harvested wild lettuce is used orally and appropriately (12,4).
LIKELY UNSAFE ...when used orally in large doses or when harvested prematurely. Large doses of wild lettuce, or prematurely harvested wild lettuce, have been reported to cause anticholinergic side effects, stupor, depressed respiration, and death (4,93563).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Valerian-Primrose Virtue. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol.
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In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.
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Theoretically, Baikal skullcap might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.
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Preliminary clinical research suggests that taking capsules containing a combination of astragalus, goldthread, and Baikal skullcap daily for 4 weeks inhibits platelet aggregation; the effect seems to be similar to that of aspirin 50 mg daily (33075). It is unclear if this effect is due to Baikal skullcap, other ingredients, or the combination.
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Theoretically, concomitant use of Baikal skullcap with antidiabetes drugs might enhance blood glucose lowering effects.
Details
Baicalein, a constituent of Baikal skullcap, has alpha-glucosidase inhibitory activity in vitro (6292). Animal research also suggests that Baikal skullcap enhances the antidiabetic effects of metformin (33408). However, in a small human study, taking Baikal skullcap extract did not enhance the antidiabetic effects of metformin, although it did modestly lower glucose levels during an oral glucose tolerance test (OGTT) (101738). Until more is known, use cautiously.
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Theoretically, concomitant use of Baikal skullcap with antihypertensive drugs might have additive effects and increase the risk of hypotension.
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Animal research suggests that baicalein, a constituent of Baikal skullcap, might lower blood pressure (33374).
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Theoretically, concomitant use of Baikal skullcap and antithyroid drugs may result in additive activity and increase the risk of hypothyroidism.
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In an animal hyperthyroid model, Baikal skullcap improved levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) (101736). The clinical significance of this effect is unclear.
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Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties.
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In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.
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Theoretically, Baikal skullcap may increase levels of drugs metabolized by CYP1A2 enzymes.
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Theoretically, Baikal skullcap might increase levels of drugs metabolized by CYP2C19 enzymes.
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In vitro evidence suggest that wogonin, a constituent of Baikal skullcap, modestly inhibits the activity of CYP2C19 enzymes (33484). This effect has not been reported in humans.
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Theoretically, concomitant use of large amounts of Baikal skullcap might interfere with hormone replacement therapy, due to competition for estrogen receptors.
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In vitro evidence suggests that Baikal skullcap has estrogenic activity (16061).
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Theoretically, Baikal skullcap might reduce lithium excretion and increase serum levels of lithium.
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Baikal skullcap is thought to have diuretic properties, which may reduce lithium excretion (5541). The dose of lithium might need to be decreased.
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Theoretically, Baikal skullcap might alter the levels and clinical effects of OATP substrates.
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Some pharmacokinetic research shows that baicalin, a constituent of Baikal skullcap, can decrease plasma levels of rosuvastatin. The mechanism is thought to involve stimulation of the activity of the organic anion-transporting polypeptide 1B1 (OATP1B1), which transports rosuvastatin into the liver. This decreases plasma levels of the drug, but increases levels at the site of action in the liver. The degree to which rosuvastatin levels are affected depends on the OATP1B1 haplotype of the individual (16395). Baikal skullcap might also affect other OATP1B1 substrates (16396,16397,16398).
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Theoretically, Baikal skullcap might increase levels of drugs transported by P-glycoprotein.
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Theoretically, taking California poppy with drugs with sedative effects may increase the risk of sedative effects.
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Theoretically, evening primrose oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Evening primrose oil contains gamma linolenic acid (GLA). There is preliminary clinical evidence that GLA can reduce platelet aggregation and prolong bleeding time (1979).
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Theoretically, evening primrose may increase the levels and clinical effects of CYP2C9 substrates.
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In vitro research shows that linoleic acid, a constituent of evening primrose oil, inhibits CYP2C9 (21017).
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Theoretically, concomitant use of lithium with evening primrose oil might decrease lithium levels and effects.
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In a case report, a patient on a stable dose of lithium for 10 years experienced a reduction in lithium levels after taking evening primrose oil 500 mg daily. Baseline levels were 0.69 mmol/L, which decreased to 0.37 mmol/L after 2 months and 0.23 mmol/L after 3 months of use. Lithium levels increased within 6 weeks of discontinuing evening primrose oil, to 0.73 mmol/L; no clinical effects were noted (96715).
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Theoretically, evening primrose oil might increase the levels and effects of lopinavir.
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In a case report, an HIV patient who took evening primrose oil (Efamol) along with lopinavir/ritonavir experienced an increase in serum levels of lopinavir to 15.2 mg/L. Six weeks after discontinuing evening primrose oil, levels of lopinavir returned to the normal range of 5-10 mg/L. When re-challenged with evening primrose oil for a week, the patient's lopinavir levels increased from 6.69 to 8.11 mg/L. It is suspected that evening primrose oil increases levels of lopinavir by inhibiting cytochrome P450 3A4 (CYP3A4), which metabolizes lopinavir (93578). However, this effect has not been reported in other research.
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Theoretically, taking evening primrose oil with phenothiazines might increase the risk of convulsions.
Details
Evening primrose oil contains gamma-linolenic acid (GLA). There is some concern that taking supplements containing GLA might cause seizures, or lower the seizure threshold, when taken with phenothiazines (88187). In one report, three patients with schizophrenia who had received phenothiazines developed EEG changes suggestive of temporal lobe epilepsy after starting treatment with GLA, although none experienced an actual seizure (21013). In another report, two patients with schizophrenia who were stabilized on phenothiazines developed seizures when evening primrose oil 4 grams daily was added. One of these patients had a prior history of seizures (21010). It is unclear whether evening primrose oil had any additive epileptogenic effects with the phenothiazines; there is no evidence that taking evening primrose oil alone causes seizures (88187).
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Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.
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Hops extract does not seem to affect the metabolism of CYP1A2 substrates.
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In vitro research suggests that flavonoid constituents of hops inhibit CYP1A2 enzyme activity (10686). However, a pharmacokinetic study in healthy postmenopausal patients shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, does not affect levels of caffeine, a CYP1A2 probe substrate (105954).
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Theoretically, hops extract might alter metabolism of CYP3A4 substrates; however, this effect may not be clinically significant.
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Animal research suggests that specific constituents of hops, called lupulones, can induce hepatic CYP3A4 enzyme activity (55325). However, a pharmacokinetic study in healthy postmenopausal patients with normal metabolism shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, decreases the concentration of alprazolam, a CYP3A4 probe substrate, by 7.6%. This reduction is unlikely to be clinically relevant (105954).
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Theoretically, concomitant use of large amounts of hops might interfere with hormone replacement therapy due to competition for estrogen receptors.
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Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.
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Theoretically, passion flower might decrease the effects of CYP3A4 substrates.
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In vitro research suggests that passion flower can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer (110704).
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Theoretically, passion flower might reduce the bioavailability of OATP2B1 and OATP1A2 substrates.
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In vitro research shows that the passion flower constituents apigenin and vitexin inhibit OATP2B1 and OATP1A2. This inhibition may be dose-dependent. One specific high-flavonoid passion flower extract (Valverde) seems to inhibit OATP2B1 and OATP1A2, while another extract with a lower flavonoid concentration (Arkocaps) shows less potent inhibition (105095). OATPs are responsible for the uptake of drugs and other compounds into the body; however, the specific activities of OATP2B1 and OATP1A2 are not well characterized.
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Theoretically, skullcap can have additive effects when used with other CNS depressants.
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Valerian can have additive sedative effects when used concomitantly with alcohol.
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Valerian has sedative effects (9894). Theoretically, valerian might have an additive sedative effect when combined with alcohol. Excessive sedation has been reported in an alcohol-abusing individual who took valerian and Gingko biloba (19426). However, the potential interaction between valerian and alcohol has been disputed in other research. Limited evidence suggests that a combination of valerian 160 mg and lemon balm 80 mg (Euvegal) does not cause further deterioration in reaction ability and reaction rate when taken with alcohol as compared to the effects of alcohol alone (19427).
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Valerian can have additive sedative effects when used with alprazolam. Also, valerian in high doses might modestly increase alprazolam levels, though this is not likely to be clinically significant.
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Valerian has sedative effects (9894). Theoretically, valerian might cause additive sedation when combined with alprazolam. Also, a small pharmacokinetic study shows that taking valerian extract 1000 mg daily (providing 11 mg valerenic acid) might increase alprazolam levels by about 19%. This might be due to valerian's mild inhibition of cytochrome P450 3A4 (CYP3A4) (13014). Despite being statistically significant, this increase is not likely to be clinically significant.
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Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.
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Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP2D6.
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Although some in vitro evidence suggests that valerian affects CYP2D6, clinical pharmacokinetic (PK) studies show that valerian is unlikely to affect the CYP2D6 enzyme (13014,13536,19430,19431). In one PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days did not affect the metabolism of dextromethorphan, a CYP2D6 substrate. In another PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of debrisoquine, an accepted CYP2D6 probe-substrate (13014,13536).
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Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP3A4.
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Although some in vitro evidence suggests that valerian extract might inhibit or induce CYP3A4, clinical pharmacokinetic (PK) studies show that valerian does not have a clinically significant effect on the CYP3A4 enzyme (6450,12214,13014,13536,19431). In one PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of midazolam, an accepted CYP3A4 probe-substrate. In another PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days modestly increases levels of alprazolam, a CYP3A4 substrate, suggesting mild inhibition of CYP3A4 (13014,13536). However, this mild inhibition is unlikely to be clinically relevant.
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Valerian might weakly inhibit glucuronidation and increase concentrations of drugs metabolized by UGT1A1 and UGT2B7.
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In vitro research shows that methanolic valerian extract and valerenic acid might competitively inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1) and UGT2B7 (81685).
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Theoretically, concomitant use with drugs with sedative effects might cause additive therapeutic effects and adverse effects (19).
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Below is general information about the adverse effects of the known ingredients contained in the product Valerian-Primrose Virtue. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, Baikal skullcap seems to be well-tolerated.
There is currently a limited amount of information on the adverse effects of intravenous and topical Baikal skullcap.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, erythema, nausea, pruritus, and vomiting.
Intravenously: Skin reactions.
Topically: Dermatitis.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity and hypersensitivity pneumonitis have been reported with a specific combination product (Limbrel, Primus Pharmaceuticals) containing extracts of Baikal skullcap and catechu.
Cardiovascular ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, elevated triglyceride levels occurred in 1 of 10 patients who received 400 mg every 8 hours and 2 of 10 patients treated with 600 mg every 8 hours, compared with 0 of 10 patients who received 200 mg every 8 hours and 0 of 6 patients who received placebo. Triglyceride elevations were considered mild and resolved after discontinuation (110023).
Dermatologic
...Orally, taking Baikal skullcap may cause erythema and pruritus (105867).
Intravenously, Baikal skullcap as part of a Tanreqing injection has been associated with reports of skin reactions in some pediatric patients (96281).
Topically, several cases of allergic contact dermatitis have been reported after applying sunscreen containing Baikal skullcap extract (105869,105870). Allergic contact dermatitis has also been reported after applying a facial cream (Resveratrol BE, Skinceuticals) containing Baikal skullcap root extract 0.5% and resveratrol 1%. Patch testing identified a positive reaction to both ingredients (110024). Baikal skullcap-induced dermatitis appears to respond to treatment with a topical corticosteroid and calcineurin inhibitor (105870).
Gastrointestinal ...Orally, use of Baikal skullcap has been associated with epigastric pain, abdominal pain, constipation, diarrhea, nausea, and vomiting (101738,105867).
Hepatic
...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of acute liver damage.
There have been at least five published reports of liver damage associated with this product. In all cases, the patients were females aged 54-68 years taking doses of 250-500 mg twice daily for 1-3 months. Signs and symptoms included jaundice, pruritus, abdominal pain, fever, rash, and elevated serum bilirubin and liver transaminase levels. All patients fully recovered and levels normalized within 3 months after discontinuation (18009,96282). In addition to these published case reports, approximately 30 liver-related adverse events have been reported to the manufacturer of this product (18009). The mechanism of hepatotoxicity is unclear (18009,18010); it is estimated that the incidence of hepatotoxicity with this product is around 1 in 10,000, although the actual incidence is unknown (18010). In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Hepatotoxicity has also been reported in two patients taking a specific dietary supplement (Move Free Advanced, Reckitt Benckiser) containing Baikal skullcap, black catechu, glucosamine, chondroitin, and hyaluronic acid (33460) and in a patient taking Baikal skullcap, elderflower, horseradish, and white willow (101737). The investigators determined that the hepatotoxicity was likely caused by Baikal skullcap in these cases (33460,101737). Additionally, cases of liver injury are reported in 4 of 37 patients taking various Kampo formulations containing Baikal skullcap and other herbs daily. Patients presented with elevated liver function tests 7 to 38 days after consumption (112179). It is unclear if this adverse effect is from Baikal skullcap, other ingredients, or the combination.
In a small study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, liver transaminase elevations occurred in 2 of 10 patients who received 400 mg every 8 hours for 6 days, compared with 0 of 6 patients who received placebo. No patients receiving either 200 mg or 600 mg every 8 hours experienced liver transaminase elevations. The elevations were considered mild and resolved after discontinuation (110023).
Pulmonary/Respiratory ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of hypersensitivity pneumonitis. Symptoms include fever, chills, headache, cough, chronic bronchitis, shortness of breath, weight loss, and fatigue. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Renal ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, proteinuria of undefined severity occurred in 1 of 10 patients who received 200 mg every 8 hours for 6 days, 3 of 10 patients who received 400 mg every 8 hours for 6 days, and 5 of 10 patients who received 600 mg every 8 hours for 6 days, compared with 1 of 6 patients who received placebo. The proteinuria was considered mild and resolved after discontinuation (110023).
General
...There is currently a limited amount of information available about the adverse effects of California poppy.
Most Common Adverse Effects:
Orally: When used in combination with hawthorn and magnesium, California poppy has been reported to cause muscular stiffness, morning fatigue, and nausea. It is not clear if these effects are from California poppy, the other ingredients, or the combination.
Gastrointestinal ...Orally, when used in combination with hawthorn and magnesium, California poppy has been reported to cause nausea (12583). It is not clear if this effect is from California poppy, the other ingredients, or the combination.
Musculoskeletal ...Orally, when used in combination with hawthorn and magnesium, California poppy has been reported to cause muscular stiffness (12583). It is not clear if this effect is from California poppy, the other ingredients, or the combination.
Neurologic/CNS ...Orally, when used in combination with hawthorn and magnesium, California poppy has been reported to cause morning fatigue (12583). It is not clear if this effect is from California poppy, the other ingredients, or the combination.
General ...Orally, cowslip in combination with other herbs is generally well tolerated (95907). Studies show it can cause gastrointestinal adverse effects and allergic skin reactions (374,379,13557).
Dermatologic ...Orally, cowslip in combination with other herbs can cause allergic skin reactions (374,379,13557).
Gastrointestinal ...Orally, cowslip in combination with other herbs can cause gastrointestinal adverse effects (374,379,13557).
General
...Orally and topically, evening primrose oil is generally well tolerated.
There is limited reliable information available regarding the safety or adverse effects of other parts of the plant.
Most Common Adverse Effects:
Orally: Abdominal pain and distention, diarrhea, dyspepsia, flatulence, nausea, and vomiting.
Dermatologic ...Orally, use of evening primrose oil has been associated with reports of skin rash and acne (9156,9794,49338). There is a case report of extensive but transient petechiae and purpuric ecchymoses in a newborn infant whose mother had consumed raspberry leaf tea and a total of 6.5 grams of evening primrose oil orally and vaginally during the week prior to delivery. The infant had a normal platelet count and no signs of hemorrhage, and was discharged healthy at 3 days of age (16303).
Gastrointestinal ...Gastrointestinal complaints, including abdominal pain, distension and fullness, nausea and vomiting, diarrhea, dyspepsia, and flatulence are the most common adverse effects of evening primrose (8926,9794,20533,49188,49286,49339,49365,65864,88184,102556). Often these effects resolve with continued use. Altered taste has also been reported (49339).
Hematologic ...There is preliminary clinical evidence that evening primrose oil can decrease platelet aggregation and prolong bleeding time. In a small study of patients with hyperlipidemia, taking evening primrose oil 3 grams daily for 4 months was associated with a 40% increase in bleeding time, and decreases in ADP- and epinephrine-induced platelet aggregation of 50% and 60% respectively (1979). There is also a case report of diffuse ecchymoses and petechiae in a neonate whose mother had consumed 6.5 grams of evening primrose oil over the week prior to delivery (16303).
Neurologic/CNS
...Cases of dizziness (9794) and headache (88184) have been reported with evening primrose oil when used orally.
There is a report of seizures in a patient taking evening primrose oil and receiving anesthesia; however, the patient was also taking other drugs and it is therefore unclear if evening primrose was the cause (613). There is also concern that evening primrose oil might cause seizures, or lower the seizure threshold, in patients with schizophrenia who are treated with phenothiazines. This is based on limited data from two studies published in the 1980s. In one report, three patients with schizophrenia who had received phenothiazines developed EEG changes suggestive of temporal lobe epilepsy after starting treatment with evening primrose, although none experienced an actual seizure (21013). In the other report, two patients with schizophrenia who were stabilized on phenothiazines developed seizures when evening primrose oil 4 grams daily was added. One of these patients had a prior history of seizures (21010). There is no evidence that evening primrose taken alone, without medications known to lower the seizure threshold, can cause seizures (88187).
Other ...Weight gain has been reported in individuals receiving evening primrose oil (49338).
General
...Orally, hops extract and oil are generally well tolerated when used in food amounts.
Hops extract also seems to be well tolerated when used in supplemental amounts.
Most Common Adverse Effects:
Orally: Drowsiness, sedation.
Dermatologic ...Topically, allergic reactions have been reported after contact with the fresh hops plant and plant dust. Contact dermatitis is attributed to the pollen (4,12,105930).
Genitourinary ...Orally, supplements containing hops and soy have been associated with 4 cases of postmenopausal bleeding (55404). It is unclear if this effect is due to hops, soy, or the combination. Also, menstrual disturbances have been reported in female workers harvesting hops (10684,55405).
Neurologic/CNS ...Orally, hops might cause drowsiness and sedation. Historically, hops are thought to have sedative effects, since workers harvesting hops were observed to tire easily after oral contact with hop resin. The European Medicines Agency states that hops may have sedative effects; however, there is a lack of clinical research confirming that hops extract causes drowsiness and sedation (105930).
Pulmonary/Respiratory ...Occupational exposure to dust from hops, usually in combination with dust from other products, is associated with chronic respiratory symptoms such as dry cough, dyspnea, chronic bronchitis, and other occupational respiratory diseases (55333,55414).
General
...Orally, passion flower is well tolerated.
Most Common Adverse Effects:
Orally: Confusion, dizziness, hypersensitivity, and sedation.
Cardiovascular ...There is a case report involving a 34-year-old female who was hospitalized with severe nausea, vomiting, drowsiness, prolonged QT interval, and episodes of nonsustained ventricular tachycardia following use of passion flower extract tablets (Sedacalm, Bioplus Healthcare), 1500 mg on day 1 and 2000 mg on day 2 to relieve stress. All symptoms resolved within one week after passion flower was discontinued (6251).
Genitourinary ...The alkaloids harman and harmaline, which are sometimes found in small amounts in passion flower, have been reported to have uterine stimulant activity (4,11020,95037).
Hematologic ...Orally, passion flower has been reported to cause epistaxis in one clinical trial (95038). Vasculitis has also been reported with use of a specific herbal product (Relaxir) produced mainly from the fruits of passion flower (6).
Hepatic ...There is debate about whether passion flower contains cyanogenic glycosides. Several related Passiflora species do contain these constituents (3), including Passiflora edulis, which is associated with liver and pancreatic toxicity (7).
Immunologic
...An idiosyncratic hypersensitivity reaction characterized by urticaria and cutaneous vasculitis has been reported in a 77-year-old male with rheumatoid arthritis after taking a specific combination product that included passion flower extract (Naturest) (68308).
It is unclear if these effects were caused by passion flower or other ingredients.
In clinical trials, passion flower has been reported to cause allergy symptoms including sinus irritation; however, the frequency of these events was statistically nonsignificant when compared to treatment with midazolam 15 mg (95038).
Musculoskeletal ...Orally, passion flower has been reported to cause muscle relaxation in a clinical trial (95038).
Neurologic/CNS ...Orally, sedation, dizziness, ataxia, and confusion have been reported in clinical trials. However, these events generally do not necessitate discontinuation (8007,15391,15392,95036,95038). Altered consciousness has been reported with use of a specific herbal product (Relaxir) produced mainly from the fruits of passion flower (6).
General
...There is currently a limited amount of information available on the adverse effects of skullcap.
Most Common Adverse Effects:
Orally: Cognitive impairment, digestive disturbances, sedation.
Gastrointestinal ...Orally, mild digestive disturbances were reported in around 9% of patients taking skullcap 350 mg three times daily for 2 weeks (91690).
Hepatic ...There are four reports of hepatotoxicity associated with products thought to contain skullcap. However, it is uncertain whether the products actually contained skullcap. It is thought that the products might have been contaminated with an adulterant such as germander (515), which is known to cause liver damage.
Neurologic/CNS ...A single skullcap extract dose of 100 mg does not seem to have adverse CNS effects. However, a higher dose of 200 mg might cause sedation and cognitive impairment (12216). One patient taking skullcap 350 mg three times daily for 2 weeks reported vivid dreams (91690). It is unclear if this event was associated with skullcap.
General
...Orally, valerian is generally well-tolerated.
Most Common Adverse Effects:
Orally: Dizziness, drowsiness, and mental slowness. Other reported side effects include headache, gastrointestinal upset, excitability, and vivid dreams. When used chronically and abruptly stopped, symptoms of withdrawal such as tachycardia, anxiety, irritability, and insomnia might occur. Advise patients to taper doses slowly after extended use.
Serious Adverse Effects (Rare):
Orally: Several case reports raise concerns about hepatotoxicity after the use of valerian and valerian-containing multi-ingredient dietary supplements. Withdrawal from chronic valerian use has been associated with cases of cardiac failure and hallucinations.
Cardiovascular ...When used orally in high doses for an extended period of time, valerian withdrawal has been associated with tachycardia and high output cardiac failure in one patient with a history of coronary artery disease (3487). Chest tightness has been reported for an 18-year-old female who took 40-50 capsules containing valerian 470 mg/capsule (659). A case of severe hypotension, suspected to be due to vasodilation, hypocalcemia, and hypokalemia, has been reported for a patient who injected an unknown quantity of a crude tap water extract of raw valerian root (81734).
Dermatologic ...Orally, valerian might rarely cause a rash. A case of valerian-related rash that resolved after valerian root discontinuation was reported in clinical research (19422).
Gastrointestinal ...Orally, valerian has been associated with increased incidence of gastrointestinal problems including diarrhea, nausea, vomiting, and stomach pain (15046,19406,19407,19422,110712). In one individual, taking 20 times the normal dose caused abdominal cramping (659).
Hepatic
...There have been several case reports of hepatotoxicity associated with the use of multi-ingredient oral preparations containing valerian (8243,96241).
In one case report, a 57-year-old man presented with acute hepatitis after consuming a cold and flu remedy containing valerian 2 grams for 3 days; the remedy also contained white willow, elderberry, and horseradish. Although the use of the cold and flu remedy was discontinued one month prior to symptom presentation, the acute hepatitis was attributed to valerian root and treated with steroids (96241). It is possible, however, that some of these preparations may have been adulterated with hepatotoxic agents (8243).
Hepatotoxicity involving long-term use of single-ingredient valerian preparations has also been reported (3484,17578). Also, a case of a 38-year-old female with liver insufficiency and cirrhosis of a vascular parenchymal nature who developed hepatotoxic symptoms following valerian and ethyl-alcohol abuse has been reported (81697). Symptoms resolved and laboratory values normalized following intense plasmapheresis treatment. Another case of acute hepatitis characterized by elevated aminotransferases, mild fibrosis, and liver inflammation has been reported for a 50-year-old female who consumed valerian root extract 5 mL three times weekly along with 10 tablets of viamine, a product containing dry valerian extract 125 mg/tablet, for 2 months (81696). Because a variety of doses were used in these cases, and many people have used higher doses safely, these hepatotoxic reactions might have been idiosyncratic. Tell patients the long-term effect of valerian on liver function is unknown.
Musculoskeletal ...In a case report, combined intake of valerian and passionflower caused throbbing and muscular fatigue when taken concomitantly with lorazepam (19429).
Neurologic/CNS ...Orally, valerian might cause dizziness, headaches, fatigue, sleepiness, and mental dullness (3484,17578,19411,19422,81723,89407). The severity of adverse effects appears to increase with higher doses (19411). However, taking valerian extracts in doses up to 1800 mg does not appear to significantly affect mood or psychomotor performance (10424,15044). Valerian does not usually have a negative impact on reaction time, alertness, and concentration the morning after intake (2074,8296). Clinical research shows that a single dose of valerian root 1600 mg is not associated with any changes in sleepiness, reaction time, or driving performance within 1-4 hours after intake (96240). More serious side effects may occur when valerian is taken at higher doses. In one individual, 20 times the normal dose caused tremor of the hand and foot and lightheadedness (659). In a case report, combined intake of valerian and passionflower caused shaking of the hands and dizziness when taken concomitantly with lorazepam (19429).
Psychiatric ...Orally, valerian has been associate with reports of restlessness, excitability, uneasiness, agitation, and vivid dreams (3484,17578,19411,19422). Chronic use and rapid cessation can lead to withdrawal syndrome with symptoms of agitation, insomnia, and hallucinations (104003). There appears to be a trend towards increased severity of adverse effects with higher doses (19411). A case of acute hypomania has been reported for a 21-year-old female patient who took a valerian decoction in water each night for one month to treat subclinical anxiety. Symptoms included euphoric mood, rapid speech, and increased sociability and sexual interest. Following cessation of valerian use and treatment with quetiapine 100 mg daily for two weeks, the patient recovered (89405). In another case report, an 85-year-old male with mild cognitive impairment, major depression, anxiety, and chronic kidney disease presented to the emergency department with hallucinations, confusion, and agitation thought to be due to abrupt cessation after taking valerian 600 mg daily for about 6 months. The symptoms resolved in about 5 days (104003).
General
...There is currently a limited amount of information on the adverse effects of wild lettuce.
Orally, large amounts of wild lettuce, as well as eating prematurely harvested wild lettuce, can cause sweating, increased respiration, tachycardia, pupil dilation, dizziness, ringing in the ears, vision disorders, pressure in the head, somnolence, excitatory states (18,93563), respiratory depression, coma, and death (4).
Topically, wild lettuce can cause contact dermatitis (4).
Intravenously, boiled wild lettuce has been reported to cause fever, severe headache, tachycardia, nausea, and abdominal pain in three intravenous drug users (93566).
Cardiovascular ...Orally, large amounts of wild lettuce or prematurely harvested wild lettuce has been reported to cause sweating, flushing, and tachycardia (18,93563).
Dermatologic ...Topically, wild lettuce can cause contact dermatitis (4). It can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.
Gastrointestinal
...Orally, wild lettuce has been reported to cause nausea, vomiting, and abdominal cramps (93563).
Intravenously, boiled wild lettuce, prepared by hand in combination with valerian root, has been reported to cause nausea and abdominal pain in three intravenous drug users (93566).
Genitourinary ...Orally, wild lettuce can cause urinary retention (93563).
Immunologic ...Intravenously, boiled wild lettuce, prepared by hand in combination with valerian root, has been reported to cause fever, severe headache, and tachycardia in three intravenous drug users. This reaction was hypothesized to be due to an immunologic response (93566).
Neurologic/CNS ...Orally, large amounts of wild lettuce or prematurely harvested wild lettuce has been reported to cause dizziness, pressure in the head, somnolence, anxiety, headache, excitatory states (18,93563), and coma (4).
Ocular/Otic ...Orally, large amounts of wild lettuce or prematurely harvested wild lettuce has been reported to cause mydriasis, pupil dilation, dizziness, ringing in the ears, and vision disorders (18,93563).
Pulmonary/Respiratory ...Orally, large amounts of wild lettuce or prematurely harvested wild lettuce has been reported to cause increased respiration (18) or respiratory depression (4).
